The unusually high production of lactate was the earliest and most outstanding biochemical characteristic discovered in cancerous tissues. It appears that pyruvate serves as the chief hydrogen acceptor for neoplastic tissues, whereas oxygen is the chief hydrogen acceptor in normal tissues. This raises the possibility that the reaction catalyzed by lactic dehydrogenase is essential in neoplastic tissues, but not in other normal resting tissues. Previous attempts by Busch and coworkers and Colowick and coworkers to develop lactic dehydrogenase inhibitors and use them as anti-cancer agents have met with some success, but problems of toxicity and lack of specificity has led to the discovery of a large family of phenolic compounds which are extremely potent, specific, non-toxic inhibitors of lactic dehydrogenase, and we have synthesized additional structural analogues which possess the same characteristic and, in some cases, surpass the natural products in potency. Preliminary tests have shown pronounced inhibition of Sarcoma 180. One aspect of the proposed research involves further detailed studies of the ability of these compounds to inhibit cancer growth. These studies will include the use of a variety of diets for the experimental tumor-bearing animals, in order to achieve maximum sensitivity of the tumor metabolic weakness. The studies will also include: (1) attempts to design even more potent inhibitors of lactic dehydrogenase, based on the information now available; (2) further analysis of the metabolism of the compounds in an effort to control this to achieve the most favorable anti-cancer activity; and (3) analysis of the various mechanisms of action of the compounds.